Although many aspects of optic pathway development are beginning to be understood, the mechanisms promoting the growth of retinal ganglion cell (RGC) axons toward visual targets remain largely unknown. Down syndrome cell adhesion molecule (Dscam) is expressed by mouse RGCs shortly after they differentiate at embryonic day 12 and is essential for multiple aspects of postnatal visual system development. Here we show that Dscam is also required during embryonic development for the fasciculation and growth of RGC axons. Dscam is expressed along the developing optic pathway in a pattern consistent with a role in regulating RGC axon outgrowth. In mice carrying spontaneous mutations in Dscam (Dscam), RGC axons pathfind normally, but growth from the chiasm toward their targets is impaired, resulting in a delay in RGC axons reaching the dorsal thalamus compared with that seen in wild-type littermates. Conversely, Dscam gain of function results in exuberant growth into the dorsal thalamus. The growth of ipsilaterally projecting axons is particularly affected. Axon organization in the optic chiasm and tract and RGC growth cone morphologies are also altered in Dscam mutants. In vitro DSCAM promotes RGC axon growth and fasciculation, and can act independently of cell contact. In vitro and in situ DSCAM is required both in the RGC axons and in their environment for the promotion of axon outgrowth, consistent with a homotypic mode of action. These findings identify DSCAM as a permissive signal that promotes the growth and fasciculation of RGC axons, controlling the timing of when RGC axons reach their targets.axon guidance | development | growth cone | optic chiasm | visual system T he developing vertebrate visual system has proven to be one of the most informative model systems for studying axon growth and guidance decision (1). In mice, retinal ganglion cell (RGC) axons grow into the brain from embryonic day (E) 12.5, although mapping within visual targets is not complete until postnatal stages (1). Molecules have been identified that are important for multiple aspects of RGC axon growth and pathfinding, including guidance out of the eye, constraining the general path followed by RGC axons and midline routing at the optic chiasm underlying the establishment of stereovision (1); however, the majority of these molecules induce inhibitory responses in RGC axons. Much less is known about the growth-promoting mechanisms that drive RGC axon extension.Down syndrome cell adhesion molecule 1 (Dscam1) is a homophilic adhesion molecule essential for multiple aspects of neural circuit formation in Drosophila, including axon growth, fasciculation, and pathfinding; dendritic field organization; and synaptic specificity and targeting (2, 3). Although vertebrate Dscam lacks the extensive alternative splicing of fly Dscam1, it is required for many of the same developmental processes, including dendritic arborization and synaptic lamination and refinement (4).Dscam is expressed by mouse RGCs from E12.5 (5) and, through regulation of cell deat...

Several aspects of the human nervous system and associated motor and cognitive processes have been reported to be modulated by extremely low-frequency (ELF, < 300 Hz) time-varying Magnetic Fields (MF). Due do their worldwide prevalence; power-line frequencies (60 Hz in North America) are of particular interest. Despite intense research efforts over the last few decades, the potential effects of 60 Hz MF still need to be elucidated, and the underlying mechanisms to be understood. In this study, we have used functional Magnetic Resonance Imaging (fMRI) to characterize potential changes in functional brain activation following human exposure to a 60 Hz MF through motor and cognitive tasks. First, pilot results acquired in a first set of subjects (N=9) were used to demonstrate the technical feasibility of using fMRI to detect subtle changes in functional brain activation with 60 Hz MF exposure at 1800 μT. Second, a full study involving a larger cohort of subjects tested brain activation during 1) a finger tapping task (N=20), and 2) a mental rotation task (N=21); before and after a one-hour, 60 Hz, 3000 μT MF exposure. The results indicate significant changes in task-induced functional brain activation as a consequence of MF exposure. However, no impact on task performance was found. These results illustrate the potential of using fMRI to identify MF-induced changes in functional brain activation, suggesting that a one-hour 60 Hz, 3000 μT MF exposure can modulate activity in specific brain regions after the end of the exposure period (i.e., residual effects). We discuss the possibility that MF exposure at 60 Hz, 3000 μT may be capable of modulating cortical excitability via a modulation of synaptic plasticity processes.

The MF used in this experiment did not affect cardiovascular parameters. Although an alternative explanation for why skin surface temperatures decreased in the sham and not in the real exposure condition is presented, the possibility of a MF effect cannot be excluded.

Extremely low frequency (ELF, <300 Hz) magnetic fields (MF) have been reported to modulate cognitive performance in humans. However, little research exists with MF exposures comparable to the highest levels experienced in occupations like power line workers and industrial welders. This research aims to evaluate the impact of a 60 Hz, 3 mT MF on human cognitive performance. Ninety-nine participants completed the double-blind protocol, performing a selection of psychometric tests under two consecutive MF exposure conditions dictated by assignment to one of three groups (sham/sham, MF exposure/sham, or sham/MF exposure). Data were analyzed using a 3 × 2 mixed model analysis of variance. Performance between repetitions improved in 11 of 15 psychometric parameters (practice effect). A significant interaction effect on the digit span forward test (F = 5.21, P < 0.05) revealed an absence of practice effects for both exposure groups but not the control group. This memory test indicates MF-induced abolition of the improvement associated with practice. Overall, this study does not establish any clear MF effect on human cognition. It is speculated that an ELF MF may interfere with the neuropsychological processes responsible for this short-term learning effect supported by brain synaptic plasticity.